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Biomedical subjects

Susan Graham

Publications and source records attributed to Susan Graham.

13 recordsLinked to original sources
PubMed2006

Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.

BACKGROUND: Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed. METHODS AND RESULTS: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction study is a National Institutes of Health-funded, randomized, double-blind clinical trial with a target enrollment of 2860 patients. It is designed to test with 90% power the 2-sided primary null hypothesis of no difference between warfarin (International Normalized Ratio 2.5-3) and aspirin (325 mg) in 3- to 5-year event-free survival for the composite endpoint of death, or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction < or =35% who do not have atrial fibrillation or mechanical prosthetic heart valves. Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and myocardial infarction (MI), balanced against the risk of intracerebral hemorrhage, among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone. Randomization is stratified by site, New York Heart Association (NYHA) heart class (I vs II-IV), and stroke or transient ischemic attack (TIA) within 1 year before randomization versus no stroke or TIA in that period. NYHA class I patients will not exceed 20%, and the study has a target of 20% (or more) patients with stroke or TIA within 12 months. Randomized patients receive active warfarin plus placebo or active aspirin plus placebo, double-blind. CONCLUSION: The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.

Anticoagulants↗
PubMed2005

Evidence for an association between heat shock protein 70 and the respiratory syncytial virus polymerase complex within lipid-raft membranes during virus infection.

In this report, the interaction between respiratory syncytial virus (RSV) and heat shock protein 70 (HSP70) was examined. Although no significant increase in total HSP70 protein levels was observed during virus infection, analysis of the HSP70 content in lipid-raft membranes from mock- and virus-infected cells revealed an increase in the levels of raft-associated HSP70 during virus infection. Fluorescence microscopy demonstrated that this transport of HSP70 into lipid-raft membranes correlated with the appearance of HSP70 within virus-induced inclusion bodies. Furthermore, co-localisation of HSP70 with the virus N protein and the raft lipid GM1 was observed within these structures. Immunoprecipitation experiments demonstrated the ability of HSP70 to interact with the virus polymerase complex in lipid-rafts in an ATP-dependent manner. Collectively, these data suggest that RSV may induce cellular changes which allow the recruitment of specific host-cell factors, via lipid-raft membranes, to the polymerase complex.

Amino Acid Sequence↗
PubMed2005

A microchip CD4 counting method for HIV monitoring in resource-poor settings.

BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.

Algorithms↗
PubMed2005

A description of a prototype miniature extracorporeal membrane oxygenation circuit using current technologies in a sheep model.

In the United States, standardization of neonatal extracorporeal membrane oxygenation (ECMO) circuit was achieved during the 1980s. Since that time, the consoles and components of the ECMO circuit have remained fundamentally unchanged (bladder, rollerpump, silicone membrane oxygenator). Extracorporeal technology, however, has witnessed many significant advancements in components during the past two decades. These new technologies have characteristics that may improve outcomes when applied in the ECMO arena. Understanding how these technologies perform in long-term applications is necessary. Therefore, the purpose of this project is to evaluate the performance of a miniature ECMO circuit consisting of current generation technologies in an animal model. An ECMO circuit (prime volume 145 mL) was designed that included a hollow fiber oxygenator and a remote mounted centrifugal pump. All circuit tubing and components were surface coated. Three sheep (approx 13 kg) were placed on ECMO using standard neck cannulation techniques and maintained according to clinical protocols. Technical implementation, oxygenator function, and hematological parameters were accessed. Duration of ECMO was 20, 48, and 58 hours. There was no evidence of oxygenator failure, as measured by pressure drop and oxygen transfer, in any of the procedures. No plasma leak was observed in any oxygenators. Platelet count trended downward after 24 hours. Visual inspection after ECMO showed very little evidence of gross thrombosis. This ECMO circuit design departs dramatically from the typical North American systems. The use of this console and components facilitated a 70% reduction in priming volume over a traditional ECMO circuit. Further investigations should be conducted to determine if circuit miniaturization can reduce the morbidity associated with blood product consumption and the bloods contact with the artificial surfaces of the ECMO circuitry.

Animals↗
PubMed2005

Design a usable protocol screening database: the user-centered approach.

Patient eligibility screening is a very important component of clinical research. Data obtained from such a task can serve valuable purposes beyond the specific protocol they are generated for and therefore should be captured and stored. We applied a user-centered design framework to evaluate the existing screening process and database at the Neurosurgery Department, M. D. Anderson Cancer Center and to design and develop a usable protocol patient screening interface.

Clinical Trials as Topic↗
PubMed2004

The small hydrophobic (SH) protein accumulates within lipid-raft structures of the Golgi complex during respiratory syncytial virus infection.

The cellular distribution of the small hydrophobic (SH) protein in respiratory syncytial virus (RSV)-infected cells was examined. Although the SH protein was distributed throughout the cytoplasm, it appeared to accumulate in the Golgi complex within membrane structures that were enriched in the raft lipid, GM1. The ability of the SH protein to interact with lipid-raft membranes was further confirmed by examining its detergent-solubility properties in Triton X-100 at 4 degrees C. This analysis showed that a large proportion of the SH protein exhibited detergent-solubility characteristics that were consistent with an association with lipid-raft membranes. Analysis of virus-infected cells by immuno-transmission electron microscopy revealed SH protein clusters on the cell surface, but only very low levels of the protein appeared to be associated with mature virus filaments and inclusion bodies. These data suggest that during virus infection, the compartments in the secretory pathway, such as the endoplasmic reticulum (ER) and Golgi complex, are major sites of accumulation of the SH protein. Furthermore, although a significant amount of this protein interacts with lipid-raft membranes within the Golgi complex, its presence within mature virus filaments is minimal.

Animals↗
PubMed2004

Evaluation of the Hemobag: a novel ultrafiltration system for circuit salvage.

Following termination of bypass, the CPB circuit contains a significant volume of diluted blood. Various methods have been used to salvage this blood, including direct transfusion or centrifugation /washing of the circuit volume. These techniques produce a reinfusion product that is either dilute or free of plasma proteins. The purpose of this study is to evaluate the Hemobag ultrafiltration system, which may overcome these limitations. Yorkshire pigs (n = 4, approximately 40 kg) were placed on CPB (prime volume 1.5 L) for 60 min. Following CPB, control blood samples (Pre) were collected from the circuit. The circuit contents were then transferred into a Hemobag and processed. Blood samples (post) were then collected from the Hemobag. Pre- and post-samples were analyzed and compared using a Student's t-test. Parameters that were significantly different (p < .05) pre-Hemobag versus post-Hemobag were as follows: hematocrit 20.4+/-3.4% vs. 54.1+/-11.6%, total protein 2.4+/-0.4 vs. 8.2+/-2.9 gms/DL, fibrinogen 92.0+/-0.3 vs. 305.8+/-37.2 mg/DL. Parameters that were not significantly different but trended toward an increase post-Hemobag were platelet counts, heparin levels, white cell count, and plasma free hemoglobin. Parameters that showed no differences or trends included sodium, potassium, chloride, bicarbonate, and osmolarity. Processing times were measured at approximately 10 minutes. This device effectively concentrates post-bypass circuit volume, providing a product that is high in red blood cells and plasma proteins and may provide an alternative to current techniques for circuit volume salvage.

Animals↗
PubMed2003

Improving the effectiveness of smoking cessation in primary care: lessons learned.

AIMS: The 'Smokescreen' smoking cessation programme was introduced in Christchurch in 1995, with an initial study showing six-month, self-reported quit rates of 10% and 17% (with a validated deception rate) in primary and secondary care settings. Substantial modifications were made to try to improve this rate in the primary care setting and the programme has been implemented widely. Our primary aim was to estimate programme utilisation and six-month quit rates for enrolled patients in this general primary care setting. We also aimed to use a wide range of patient, practice and environmental variables to estimate any predictive effect on outcome. METHODS: Prospective longitudinal cohort study. The nicotine replacement therapy (NRT) -based programme was implemented by Pegasus Health, an independent practitioner association (IPA) situated in the Christchurch urban area, to which the majority of Christchurch-based GPs belong. A cohort of 516 patients enrolling in the programme over a two-month period were contacted six months after their nominated quit date. The main outcome measure was the six-month, self-reported quit rate. RESULTS: Of the 516 participants, 334 (65%) were contacted by mail or telephone. The overall six-month quit rate was 36% (95% Confidence Interval (CI) 31-41). Univariate analysis initially showed duration of NRT (p = 0.03) and age band (p = 0.004) were significant predictors of quitting, while living with a smoker (p = 0.02), having made no previous quit attempts (p = 0.02) and having heart disease (p = 0.01) were all significant predictors of continued smoking at six months. Factors that did not predict whether respondents were smoking at six months included previous use of NRT, sex, ethnicity, who delivered the intervention, years of smoking, cigarette dose, and NZDep96 score. However, there was interaction between these factors as after multivariate analysis the only significant predictors of outcome were having others living in the house who smoked (odds ratio (OR) 0.55, 95% CI 0.33--0.93, p = 0.03) and having made no previous quit attempts (OR 0.29, 95% CI 0.12-0.71, p = 0.02). Both these factors were significantly associated with continuing to smoke. CONCLUSIONS: This programme compares favourably with six-month quit rates for NRT-based programmes reported in the international literature of 14-22%. The effectiveness of an NRT-based smoking cessation programme in a general primary care setting appears to have been significantly enhanced by local adaptation, the flexibility of a primary-care-team approach and subsidisation of NRT, together with facilitation responsive to individual practice needs. The success of this programme in helping individual patients quit, as well as its successful implementation in a wide primary care setting, suggests General Practice can play an important role in smoking cessation in a country with a high burden of disease from smoking-related illnesses. The programme is congruent with the current, national, smoking cessation guidelines endorsed by the RNZCGP. Widespread adoption of this kind of model in IPA/primary health organisation (PHO) settings throughout New Zealand should be encouraged and supported.

Adolescent↗
PubMed2002

Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles.

Purification of hepatitis C virus (HCV) from sera of infected patients has proven elusive, hampering efforts to perform structure-function analysis of the viral components. Recombinant forms of the viral glycoproteins have been used instead for functional studies, but uncertainty exists as to whether they closely mimic the virion proteins. Here, we used HCV virus-like particles (VLPs) generated in insect cells infected with a recombinant baculovirus expressing viral structural proteins. Electron microscopic analysis revealed a population of pleomorphic VLPs that were at least partially enveloped with bilayer membranes and had viral glycoprotein spikes protruding from the surface. Immunogold labeling using specific monoclonal antibodies (MAbs) demonstrated these protrusions to be the E1 and E2 glycoproteins. A panel of anti-E2 MAbs was used to probe the surface topology of E2 on the VLPs and to compare the antigenicity of the VLPs with that of truncated E2 (E2(660)) or the full-length (FL) E1E2 complex expressed in mammalian cells. While most MAbs bound to all forms of antigen, a number of others showed striking differences in their abilities to recognize the various E2 forms. All MAbs directed against hypervariable region 1 (HVR-1) recognized both native and denatured E2(660) with comparable affinities, but most bound either weakly or not at all to the FL E1E2 complex or to VLPs. HVR-1 on VLPs was accessible to these MAbs only after denaturation. Importantly, a subset of MAbs specific for amino acids 464 to 475 and 524 to 535 recognized E2(660) but not VLPs or FL E1E2 complex. The antigenic differences between E2(660,) FL E1E2, and VLPs strongly point to the existence of structural differences, which may have functional relevance. Trypsin treatment of VLPs removed the N-terminal part of E2, resulting in a 42-kDa fragment. In the presence of detergent, this was further reduced to a trypsin-resistant 25-kDa fragment, which could be useful for structural studies.

Amino Acid Sequence↗
PubMed2002

Comparison of five point-of-care prothrombin and activated partial thromboplastin time devices based on age of blood sample.

Delays in processing statium (STAT) blood samples have led to the production of an increasing number of point-of-care tests. Product inserts recommend measuring blood samples immediately after procurement, suggesting that delays may invalidate the test results. We studied the effect of the age of blood samples on point-of-care (POC) prothrombin time (PT) and an activated partial thromboplastin time (aPTT) result. Informed consent was obtained from 11 patients undergoing cardiopulmonary bypass (CPB). Blood samples (40 mL) were taken from each patient. Each blood sample was used to perform five PT tests and six aPTT tests on five POC devices (Gem PCL, Hemochron 801, Hemochron Jr. Signature, Hemochron Response, Rapidpoint Coag) at three different sample ages [< 60 s (fresh blood), 10 and 18 min after sample collection]. Blood samples were procured in a plastic syringe devoid of air bubbles, which was left undisturbed between tests but was gently agitated before initiating the 10- and 18-min tests. For tests requiring citrated whole blood, a fraction of each sample was anticoagulated (3.8% citrate) at each age. Statistical analysis was used for comparison of test results for fresh blood to aged samples (10 and 18 min). Test values were recorded as International Normalized Ratio (INR) and seconds for PT and aPTT, respectively. Two devices, the Hemochron 801 and Hemochron response showed statistically, although not clinically, significant variation in PT test results when the samples were aged to 10 and 18 minutes. As for aPTT results, Hemochron 801, Hemochron response, Hemochron Jr. signature, and Gem PCL showed statistically significant variation at 18 minutes. One device (Hemochron 801) reported results with 10-min aged blood that were statistically different from fresh blood. None of the aPTT tests results from any device produced results with aged blood that were clinically different from fresh blood. This study suggests that, in the tests evaluated, blood samples that have aged 10 or 18 min will produce clinically relevant aPTT and PT results, respectively.

Adult↗
PubMed2002

Electronic data management for the Hemochron Jr. Signature coagulation analyzer.

Point-of-care testing (POC, POCT) laboratory devices are being introduced into operating suites and critical care units in ever increasing numbers. The small, portable devices have gained in popularity because of their ease of use and the rapid availability of test results. POCT is an integral part of extracorporeal technology (ECT). A challenge associated with the growth of POC technology is related to management of the data generated by these devices. In the field of ECT, storing, retrieving, analyzing, viewing and charting quality control (QC) and patient test data generated with POC coagulation instruments is essential. We evaluated a premarket version of data management software developed for the Hemochron Jr. Signature coagulation analyzer, a PC-based software capable of fulfilling our objective. A database comprised of greater than 50 plasma and electronic QC results and greater than 140 patient sample results for ACT, PT, and aPTT tests was transferred from a Hemochron Jr. Signature device to two different PCs, each equipped with Hemochron ReportMaker software supplied by the manufacturer. Data files were transferred directly from the coagulation test unit to the PCs via an RS-232 cable. A variety of charts, reports, and file listings were created from the datasets using the software menus. Transfer of the complete database required less than 5 min. The relative speed and simplicity of the data interface promotes frequent charting of QC data, permitting real-time monitoring and early identification of data trends or values requiring intervention. If a subset of QC data is found to be incomplete, altered, or unacceptable, all patient samples tested during that period can be promptly identified. The software also includes data query tools useful for sorting and selecting specific subsets of patient and QC data. Electronic data management can facilitate compliance with quality control requirements and assist clinicians and laboratory personnel in the collection, storage, and review of quality control and patient test data. In addition, the patient and QC data are readily accessible when necessary for use in risk management assessment, accreditation, or litigation proceedings.

Blood Coagulation Tests↗